As one of the primary ligands for the T cell receptor, the Class II major histocompatibility antigens are uniquely suited to control both the differentiation and activation of T cells. Differences in Ia expression can confer unique capabilities to delete self-reactive T cells in the thymus, or to initiate lymphokine cascades in the periphery. Both of these important for immune surveillance of tumors, infectious agents and soluble antigens. Therefore our ability to modulate the immune response to a variety of antigens ultimately relies on our understanding of class II gene regulation. The goal of this proposal is study the coordinate regulation of multiple class II genes among themselves and with the invariant chain gene. Accumulative evidence suggests that class II genes and invariant gene share some homologous elements. Conversely, some class II genes also have unique regulatory elements. All of the regulatory elements can interact with nuclear proteins which are presume transcription factors. The objectives of this proposal are to determine if DNA-binding proteins that regulate one class II gene (DRalpha) also regulates various other class II genes, as well as the invariant chain gene. To achieve this, relevant DNA binding proteins will also be used. The ability of each DNA binding protein with specificity for the DRalpha gene to control multiple class II genes as well as the invariant chain gene in a coordinate fashion will be assessed. This type of functional analysis will definitely determine if class II genes are coordinately regulated due to shared specificity for DNA-binding proteins.